PDUS Scores Research Articles

P217 Describing the evolution of concordance/discordance between DAS28-ESR and ultrasound power Doppler synovitis in a treatment-naïve early RA cohort

Abstract Background/Aims Discordance between DAS28-ESR and ultrasound (US)-detected power Doppler synovitis (PDUS) can lead to unnecessary DMARD cycling. Using DAS28-ESR and PDUS in an early RA trial cohort, we aimed to identify and describe concordance and discordance at diagnosis and evaluate their proportional change in response to treatment. Methods The ‘VEDERA’ trial randomised 120 treatment-naïve, new-onset RA patients to first-line etanercept + methotrexate (ETN+MTX) or methotrexate treat-to-target (MTX-TT) with escalation to ETN+MTX if not in DAS28-ESR remission at week 24. Clinical and US assessments were completed at baseline, weeks 12/24/48. Remission was DAS28-ESR ≤2.6 and active disease was DAS28-ESR >2.6. PDUS presence was defined as total PDUS score ≥ 1. Active concordance was defined as active disease with PDUS while active discordance was defined as active disease without PDUS. Remission concordance was defined as remission without PDUS while remission discordance was defined as remission with PDUS. Descriptive analyses were undertaken to address the above aims. Results At baseline all patients had active disease - 67% (81/120) were concordant and 33% (39/120) were discordant. Baseline DAS28-ESR and individual components were higher in the concordant compared to discordant group. In the active concordant group, from baseline to weeks 24 and 48 respectively, 30% (24/81) and 20% (16/81) persisted, and 26% (22/81) and 38% (31/81) became remission concordant; while 30% (24/81) and 35% (28/81) shifted to active discordance at weeks 24 and 48 respectively and 14% (11/81) and 7% (6/81) became remission discordant. In the active discordant group, from baseline to weeks 24 and 48 respectively, 72% (28/39) and 49% (19/39) persisted and only one and two patients were remission discordant; while 8% (3/39) and 15% (6/39) shifted to active concordance at weeks 24 and 48 respectively and 18% (7/39) and 31% (12/39) became remission concordant. Conclusion Discordance of DAS28 is typically associated with later RA. In this report, a third of patients shifted from active concordance to discordance following DMARD treatment early in the RA pathway. Further study is needed to understand how these patients compare to those that started and persisted with active discordance, and also later discordant RA patients. Disclosure R. Shukla: None. D.A. Selby: None. P. Emery: None. D. Plant: None. M.H. Buch: None.

Ultrasound and multi-biomarker disease activity score for assessing and predicting clinical response to tofacitinib treatment in patients with rheumatoid arthritis

BackgroundMusculoskeletal ultrasound (MSUS) and the multi-biomarker disease activity (MBDA) score are outcome measures that may aid in the management of rheumatoid arthritis (RA) patients. This study evaluated tofacitinib response by MSUS/MBDA scores and assessed whether baseline MSUS/MBDA scores or their early changes predict later clinical response.MethodsTwenty-five RA patients treated with tofacitinib were assessed at baseline, 2, 6 and 12-weeks. Power doppler (PDUS) and gray scale (GSUS) ultrasound scores, MBDA score, clinical disease activity index (CDAI), and disease activity score (DAS28) were obtained. Pearson correlations and multiple linear regression models were used to evaluate associations and identify predictors of response to therapy.ResultsMSUS, MBDA scores, CDAI, and DAS28 improved significantly over 12 weeks (p < 0.0001). Baseline MSUS and MBDA score correlated with each other, and with 12-week changes in CDAI/DAS28 (r = 0.45–0.62, p < 0.05), except for GSUS with DAS28. Two-week change in MSUS correlated significantly with 12-week changes in CDAI/DAS28 (r = 0.42–0.57, p < 0.05), except for early change in PDUS with 12-week change in CDAI. Regression analysis demonstrated significant independent associations between baseline PDUS/MBDA score and 6-week change in CDAI/DAS28, with adjustment for baseline CDAI/DAS28 (all p < 0.05); and between baseline MBDA scores and 12-week change in DAS28 (p = 0.03).ConclusionsRA patients treated with tofacitinib for 12 weeks demonstrated improvement by clinical, imaging, and biomarker end-points. Baseline PDUS and MBDA score were predictive of CDAI and DAS28 responses. This is the first study to evaluate early measurements of MSUS and MBDA score as predictors of clinical response in RA patients treated with tofacitinib.Trial registrationClinicalTrials.gov NCT02321930 (registered 12/22/2014).

Absence of correlation between DAS28-ESR, DAS28-CRP, SDAI, CDAI and ultrasound scoring in patients with rheumatoid arthritis in remission

Objective: Several composite scores (28-joints Disease Activity Score (DAS28), Simplified/Clinical Disease Activity Index (SDAI/CDAI)) may be used as target of therapeutic strategies in rheumatoid arthritis (RA) management. Although ultrasound (US) is a useful imaging technique in RA management, there are no validated US remission criteria. We aimed at analyzing correlations between US and clinical scores in RA patients with clinical remission. Methods: This French multicenter cross-sectional study, in 11 Rheumatology departments, consecutively included patients from August 2015 to April 2016. Inclusions criteria were: RA diagnosis meeting ACREULAR 2010 criteria, <15 years of progression, DAS28-ESR<2.6 for at least 3 months, stable treatment for at least 6 months, including steroids if necessary. Correlations between US scores (Naredo12 B-mode, PD-mode, combined B+PD mode, PDUS scores) and clinical remission composite scores (DAS28-ESR (Erythrocyte Sedimentation Rate), DAS28-CRP (C Reactive Protein), SDAI, CDAI) were analyzed. Results: 225 patients were analyzed. Intra/inter-observer reliabilities were good to excellent. Correlations between clinical and US Naredo12 scores were weak to moderate, with correlation coefficients ranging from 0.086 [-0.05; 0.21] to 0.323 [0.20; 0.44]. Best correlations were observed between PD-mode and SDAI or CDAI. US Naredo12 PD-mode score of 0/36 predicts a SDAI remission with 78% sensitivity and 49% specificity (area under curve 0.65). No association was found between US Naredo12 scores and type of treatment, remission duration or disease duration. Conclusions: There is no strong correlation between US and clinical scores in remission RA patients in routine care. US input in the definition of RA remission remains uncertain.

The relationship between US7 ultrasound joint scoring system and disease activity score DAS28 in rheumatoid arthritis: A study in Indian population

Introduction: US7 (7 joint ultrasound score) is an emerging ultrasound (US) joint scoring system for the assessment of disease activity in patients with Rheumatoid Arthritis (RA). Methods and Material: The study was conducted at a tertiary care center in Southern India. Sixty-two patients of RA were recruited for this cross-sectional observational study. Patients' clinical & laboratory parameters were used to calculate the disease activity score DAS28. Grayscale and Power Doppler Ultrasound (GSUS & PDUS) were performed to calculate US7 score.Statistical analysis used: Spearman's rank-order correlation, Pearson interclass correlation and ROC (receiver operating characteristic) curve analysis were performed. Results: Median DAS28 value was 4.04 with one patient in clinical remission. There was a statistically significant positive correlation (r=0.262) between synovitis by GSUS score & DAS 28 (p-value = 0.040) and synovitis by PDUS score and DAS 28 (r=0.340, p-value = 0.004). No significant correlation was found between DAS28 and tenosynovitis or erosions score. ROC curve analysis yielded the p values of 0.04 and 0.004 for synovitis by GSUS and synovitis by PDUS respectively in differentiating between the patients with low (DAS groups 1 & 2) and high disease activity (3 & 4). Conclusions: There is good correlation of the synovitis component of US7 score with DAS28. However, relationship of tenosynovitis and erosions with disease activity is questionable according to our results. An 'abbreviated US7' score with detection of only synovitis may be more suitable. This requires further validation.

Linking systemic angiogenic markers to synovial vascularization in rheumatoid arthritis.

BackgroundNeoangiogenesis is a crucial event to promote the development of the hyperplasic proliferative pathologic synovium in Rheumatoid arthritis (RA). Ultrasound (US) is sensitive for detection of power Doppler (PD) vascularization.ObjectiveTo explore the associations between a set of complementary circulating angiogenic markers and a comprehensive US assessment in patients with RA.Patients and methodsSerum levels of eight angiogenic markers were measured by quantitative ELISAs in a total of 125 patients with RA, who were all systematically assessed in parallel by PDUS, performed on 32 joints.ResultsSerum levels of soluble Vascular Cell Adhesion Molecule-1 (sVCAM-1) and Tie-2 were more likely to be increased in patients with synovial hyperemia detected on at least one joint (Power Doppler grade ≥1). sVCAM-1, Tie-2 and Angiostatin concentrations gradually increased together with the grade of the semiquantitative PDUS scale and concentrations of these three markers were markedly increased in patients with moderate to marked hyperemia (Power Doppler grade 2 and 3). Levels of sVCAM-1, Tie-2, and Angiostatin correlated with a global arthritis sum score, defined by the sum of the semiquantitative PDUS scores for all joints examined. Levels of Tie-2 and Placenta Growth Factor (PlGF) were associated with PDUS features indicating residual disease activity.ConclusionOur results support the relevance of measuring serum levels of vascular markers to evaluate the intensity and extent of synovial vascularization. Angiogenic markers, and particularly Tie-2, could be a valuable surrogate of active synovitis and their place in relation to PDUS in clinical practice deserve further investigation.

Synovial Predictors of Differentiation to Definite Arthritis in Patients With Seronegative Undifferentiated Peripheral Inflammatory Arthritis: microRNA Signature, Histological, and Ultrasound Features.

Objectives: To examine synovial tissue (ST) predictors of clinical differentiation in patients with seronegative undifferentiated peripheral inflammatory arthritis (UPIA).Methods: Fourty-two patients with IgA/IgM-Rheumatoid Factor and anti-citrullinated peptide antibodies negative UPIA, naive to Disease-Modifying Anti-Rheumatic Drugs, underwent Gray Scale (GSUS) and power Doppler (PDUS) evaluation and Ultrasound (US) guided ST biopsy. CD68, CD3, CD21, CD20, and CD31 synovial expression was evaluated by immunohistochemistry. Whole ST microRNA expression was assessed using miScript miRNA PCR Array. Peripheral blood (PB) and synovial fluid (SF) IL-6, VEGF-A, and VEGF-D levels were measured by ELISA and ST TNF expression was assessed by RT-PCR. Each patient was prospectively monitored and classified at baseline and within 1 year as UPIA, Rheumatoid Arthritis (RA), Spondyloarthritis (SpA) or Psoriatic Arthritis (PsA), respectively.Results: At baseline, CD68+ cells were the most common cells within the lining layer (p < 0.001) in seronegative UPIA, directly correlating with GSUS (R = 0.36; p = 0.02) and PDUS (R = 0.55; p < 0.001). Synovial CD31+ vessels count directly correlated with GSUS (R = 0.41; p = 0.01) and PDUS (R = 0.52; p < 0.001). During the follow-up, 6 (14.3%) UPIA reached a definite diagnosis (2 RA, 2 SpA and 2 PsA, respectively). At baseline, UPIA who differentiated had higher GSUS (p = 0.01), PDUS scores (p = 0.02) and higher histological scores for CD68+ (p = 0.005 and p = 0.04 for lining and sublining respectively), sublining CD3+ cells (p = 0.002), CD31+ vessels count (p < 0.001) and higher IL-6 PB levels (p = 0.01) than patients who remained as UPIA. MiRNA PCR Array showed that among the 86 tested miRNA species, at baseline, miR-346 and miR-214 were significantly down-regulated (p = 0.02 for both) in ST of UPIA who differentiated than in patients who remained as UPIA, inversely correlating with the lining CD68+ cells IHC score (R = −0.641; p = 0.048) and CD31+ vessels count (R = −0.665; p = 0.036) and with higher baseline ST expression of TNF (p = 0.014). Finally, logistic regression analysis demonstrated that baseline GSUS and PDUS scores ≥1.5 [OR:22.93 (95%CI:0.98–534.30)] and CD31+ vessels count ≥24.3 [OR:23.66 (95%CI:1.50–373.02)] were independent factors associated with the development of definite arthritis.Conclusions: MiRNA signature, histological and US features of ST may help in the identification of seronegative UPIA with high likelihood of clinical differentiation toward definite seronegative arthritis.

Relationships between ultrasound enthesitis, disease activity and axial radiographic structural changes in patients with early spondyloarthritis: data from DESIR cohort

BackgroundTo search for association between ultrasound (US) enthesis abnormalities and disease activity, spine and sacro-iliac joints (SIJ) MRI inflammatory lesions and spine structural changes in a cohort of patients suspected...

Role of ultrasound disease activity score in assessing inflammatory disease activity in rheumatoid arthritis patients

Aim of the workTo evaluate role of ultrasound disease activity score (DAS) in assessing joint inflammation in rheumatoid arthritis (RA), and its correlation with disease parameters. Patients and methodsFifty RA were included. All patients were assessed for DAS-28, health assessment questionnaire disability index (HAQ-DI) and X-ray simple erosion narrowing score (SENS). Power Doppler (PD) and grey-scale (GS) US examination were done for all patients. PDUS score for synovitis in 22 joints and GS score for effusion/hypertrophy in 28 joints were included in US DAS calculation. ResultsThe mean age of the patients was 43.9±10.8years; 46 females and 4 males and the mean disease duration was 8.7±6.1years. The mean DAS28 was 5.04±1.2 and HAQ-DI was 1.2±0.7. The mean US DAS was 5.2±1.3 (2.11–7.21). According to the US DAS, patients with high activity had significantly prolonged morning stiffness, higher swollen and tender joint counts, patient and physician global assessment, DAS-28, HAQ-DI, and SENS compared to those with moderate activity or low activity/remission. The mean US erosion count (USEC) was 8.9±6.6 (0–18) and it was higher in patients with high disease activity (p=0.04). A significant correlation was found between USDAS with DAS28 and HAQ-DI. US DAS showed moderate correlation (r=0.5, p=0.001), while USEC showed a strong correlation (r=0.8, p<0.001) with SENS. ConclusionUS DAS is a feasible scoring system for use in daily rheumatologic practice. US DAS may reflect disease activity and disability. The association between US DAS and USEC with radiologic scoring reflects their ability to detect structural joint damage.

Joint-specific assessment of swelling and power Doppler in obese rheumatoid arthritis patients

BackgroundClinical swollen joint examination of the obese rheumatoid arthritis (RA) patient can be difficult. Musculoskeletal Ultrasound (MSUS) has higher sensitivity than physical examination for swollen joints (SJ). The purpose of this study was to determine the joint-specific association between power Doppler (PDUS) and clinical SJ in RA across body mass index (BMI) categories.MethodsCross-sectional clinical and laboratory data were collected on 43 RA patients. PDUS was performed on 9 joints (wrist, metacarpalphalangeal 2–5, proximal interphalgeal 2/3 and metatarsalphalangeal 2/5). DAS28 and clinical disease activity index (CDAI) were calculated. Patients were categorized by BMI: <25, 25–30, and >30. Demographic and clinical characteristics were compared across BMI groups with Kruskal-Wallis test and chi-square tests. Joint-level associations between PDUS and clinically SJ were evaluated with mixed effects logistic regression models.ResultsWhile demographics and clinically-determined disease activity were similar among BMI groups, PDUS scores significantly differed (p = 0.02). Using PDUS activity as the reference standard for synovitis and clinically SJ as the test, the positive predictive value of SJ was significantly lower in higher BMI groups (0.71 in BMI < 25, 0.58 in BMI 25–30 and 0.44 in BMI < 30) (p = 0.02). The logistic model demonstrated that increased BMI category resulted in decreased likelihood of PDUS positivity (OR 0.52, p = 0.03).ConclusionsThis study suggests that in an obese RA patient, a clinically assessed SJ is less likely to represent true synovitis (as measured by PDUS). Disease activity in obese RA patients may be overestimated by CDAI/DAS28 calculations and clinicians when considering change in therapy.

Cryotherapy decreases synovial Doppler activity and pain in knee arthritis: A randomized-controlled trial

ObjectiveTo measure and compare the effects of 2 local cryotherapy techniques on synovial power Doppler activity (primary outcome) and pain in non-septic knee arthritis without any concurrent treatment. Methods30 patients were randomized (ice: 30min, n=15 or cold CO2: 2min, n=15 both applied twice at 8h interval). Contralateral non-treated arthritic knees were used as paired controls (n=11 and n=10 respectively). The PDUS semi-quantitative score (0–3) and pain visual analogic scale were evaluated before/after each cold application, 2min, 2h, 24h after the first application. PDUS scores were checked in double-blind by 2 ultrasonographists. ResultsThe inter-class effect size of local cryotherapy on the power Doppler score remained significant the day after treatment in local cryotherapy-treated compared to contralateral non-treated knees (Global difference: −1 [95% confidence interval: −1.23; −0.77]; ice: −0.73 [−1.06; −0.4]; CO2: −0.7 [−1.18; −0.22]). Both techniques significantly and to the same extent reduced the power Doppler score and pain visual analogic scale at all evaluation times and globally throughout the 24 hour-study period. No dropout nor adverse event was reported. In multivariate analysis, the Power Doppler score decrease was associated with pain decrease, while pain decrease was associated with the female sex and ice technique. ConclusionLocal ice and cold CO2 applied twice equally reduced synovial Power Doppler activity and pain over 24h in knee arthritis. These effects remained significant the day after treatment. ClinicalTrials.gov identifier: NCT02573298.

First step in the development of an ultrasound joint inflammation score for rheumatoid arthritis using a data-driven approach

ObjectivesTo develop and validate candidate sets of joints and tendons for assessment of ultrasound (US) joint inflammation in rheumatoid arthritis (RA).MethodsPatients were included in one of two cohorts from 2010...

AB0430 Effects of Abatacept and TNF Inhibitors Compared with Ultrasonography in Patients with Rheumatoid Arthritis

ObjectivesThe present study aimed to compare the effects of abatacept (ABT) and tumor necrosis factor inhibitors (TNFi) against rheumatoid arthritis (RA).MethodsPatients with RA were treated with ABT (n=51) or TNFi...

SAT0208 Seven-Joint Power Doppler Ultrasound Score is Discordant to DAS28, SDAI and CDAI in Treatment Target Identification in Rheumatoid Arthritis Patients with Fibromyalgia

BackgroundFM increases DAS28, SDAI and CDAI, misleading DMARD use and increasing costs and adverse events. (1,2) Seven-joint PDUS score is an objective measure of RA activity and, therefore, should not...

AB0728 Comparison of effects of standard- and low-dose etanercept on inflammatory synovitis in rheumatoid arthritis patients as assessed by ultrasonography

ObjectivesThe presence of synovitis has been recognized as one of the most important predictive factors of subsequent structural damage in patients with rheumatoid arthritis (RA). We previously reported that the...

SAT0514 Associations between Functional Status and Ultrasound – Detected Synovitis and Joint Damage in Rheumatoid Arthritis during Tocilizumab Treatment

BackgroundPhysical function is one of the major outcomes in rheumatoid arthritis (RA) which can predict work disability, quality of life and mortality. It has been shown that multiple factors are...

AB0510 Monitoring disease activity and response through power doppler ultrasonography in rheumatoid arthritis patients treated with rituximab – correlations with antibodies pannel

BackgroundRituximab is a a chimeric anti-CD20 monoclonal antibody approved to reduce the signs and symptoms of moderately to severely active rheumatoid arthritis (RA) in patients with inadequate response to first...

SAT0277 Clinical Response in Early Psoriatic Arthritis may be Predicted by Rapid Reduction of a Semiquantitative Ultrasound Synovitis Score

BackgroundAccurate monitoring of disease activity in early PsA is limited by the potential underestimation of inflammation by clinical examination and the absence of disease-specific biochemical markers. Therefore, sensitive and reliable...

SAT0488 Sensitivity to Change of a Combined Gray-Scale and Power Doppler Ultrasound Score for Synovitis in Comparison to a Sum Score of 5 Joints of the Wrist and Hand – One-Year Evaluation of an RA Cohort.

BackgroundSeveral ultrasound (US) scoring systems have been proposed for evaluating objectively RA patients’ responsiveness under treatment [1-3].ObjectivesTo evaluate the sensitivity to change over one year of a combined gray-scale (GS)...

FRI0509 Validation of a novel photo optical imaging (lightscan) in patients with rheumatoid arthritis and osteoarthritis using musculoskeletal ultrasound as reference

BackgroundThe lightscan is a novel imaging technology to assess inflammatory activity in proximal interphalangeal (PIP) joints.ObjectivesTo compare the lightscan method with musculoskeletal ultrasound (US) and the clinical disease activity score...

THU0434 Three-dimensional power doppler sonographic evaluation of finger joints in patients with rheumatoid arthritis

BackgroundThe accurate assessment of joint inflammation and sensitive monitoring of the disease activity in rheumatoid arthritis (RA) patients are vital to assess the disease outcome and treatment response.In the past...